The screening of large numbers of chemical compounds bfor pharmaceutical, toxicological, genetic or other types of activity is a technique that is widely used by scientists and researchers. For example, in searching tbr compounds that might have usefulness as new drugs, a researcher may want to determine if a compound shows any sign of binding to or reacting with another biological molecule, so as to decrease or increase the activity of the biomolecule. This type of screening is used, for example, in small-molecule drug discovery.
To do this, the researcher needs to evaluate how one or more test compounds react with a large number of target compounds. This means that pharmaceutical companies, universities and other research organizations need to maintain very large libraries of target compounds for high throughput screening. The library size can range from the low hundreds of thousands to tens of millions of chemical compounds. Each of these compounds must be cataloged, stored, sampled, distributed and tracked. Not only are the logistics of tracking a large chemical library challenging, but the quality of the chemical samples in the library must also be monitored.
Initially, the individual compounds in the chemical library are usually obtained as solids, films or beads. A master copy of the compound is then prepared as a concentrated solution in an organic solvent, which is usually dimethyl sulfoxide (DMSO), and is stored in a compound storage tube. Replicates (or daughters) of the master copy are prepared and distributed to end users. The end user may consider the daughter solution as a local master and prepare a low volume working copy of the compound by transferring a small volume of the local master to another storage container, such as a polypropylene microtube or microplate. The concentration of the compound in the working copy could be, for example, ten millimolar (10 mM) for small molecule compounds, or 200 mM for fraction libraries. Small volumes of the working copy of the compound are constantly removed from the storage container as the researcher prepares samples for use in an assay. This use exposes the working copy to common laboratory contaminants such as light, water vapor, dust and oxygen, and gradually causes the quality and/or concentration of the working copy to change.
Water vapor is a major problem for samples stored in DMSO. DMSO is very hygroscopic, and it is not unusual for the concentration of working copies to decrease by as much as 20% or more while being used because of water dilution. Water uptake by DMSO also causes freezing point depression, which can cause quicker degradation of samples when being stored at low temperatures. Consequently, it is necessary to periodically check the working sample to determine the concentration of water in the working sample.
Several methods for determining the water content (hydration) of DMSO are known in the prior art. An older method is the Karl Fischer titration technique. Newer methods include acoustic methods and optical methods, such as fluorescence techniques and absorption techniques. For example, an optical approach to determining the water content in DMSO for a corporate compound collection is described in Semin et al., A Novel Approach to Determine Water Content in DMSO for a Compound Collection Repository. Journal of Biomolecular Screening 10(6), pp. 568-572 (2005). This approach uses near-infrared (NIR) spectroscopy to analyze the absorption bands of water present in the DMSO. This approach is desirable because it is accurate and nondestructive. However, the instrumentation used in this technique, especially the spectrometer, means that it is relatively expensive and not easily integrated into a lab automation system.
What is needed is a technique for measuring the water content in DMSO solutions or other organic solvent solutions that is casily integrated into a lab instrument, a handheld device or an automation system while being inexpensive, last and having low power requirements. Additionally, the measurements should be taken directly in the storage vessel holding the DMSO or other solvent solution without destroying or contaminating any of the solution.